Deltonin induces apoptosis in MDA‑MB‑231 human breast cancer cells via reactive oxygen species‑mediated mitochondrial dysfunction and ERK/AKT signaling pathways.

Abstract

Deltonin, a steroidal saponin isolated from Dioscorea zingiberensis Wright, exhibits high cytotoxic activity in cancer cells. In the present study, the effects of deltonin on cell proliferation and apoptosis were evaluated in the MDA‑MB‑231 human breast carcinoma cell line. Following treatment with deltonin, the viability of MDA‑MB‑231 cells was analyzed using MTT assay and apoptosis, mitochondrial membrane potential (∆Ψm) alternation and intracellular reactive oxygen species (ROS) generation was determined by flow cytometry. In addition, western blot analysis was performed to examine the expression of apoptosis‑associated proteins. The results demonstrated that deltonin induced apoptosis in MDA‑MB‑231 cells in a time‑ and concentration‑dependent manner. Apoptosis was associated with depolarization of ∆Ψm and time‑dependent ROS generation. Deltonin treatment also resulted in Bax upregulation, Bcl-2 downregulation, activation of caspase‑3 and ‑8 and poly (ADP ribose) polymerase cleavage. Decreased levels of phosphorylated extracellular signal‑regulated kinase (ERK) and phosphorylated AKT were also observed. Results indicate that the proliferation inhibitory effect of deltonin is associated with its apoptosis‑inducing effect, which may correlate with ROS‑mediated mitochondrial dysfunction as well as activation of the ERK/AKT signaling pathways. Therefore, deltonin may be a potential chemotherapeutic agent for the treatment of breast cancer.

• Authors: Shiyuan Zhang, Yang He, Qingyi Tong, Qianming Chen, Xiaohua Wu, Wen Huang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 7 Issue 3 Pg. 1038-44 (Mar 2013) ISSN: 1791-3004 [Electronic] Greece
• PMID: 23314115 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• Spirostans
• bcl-2-Associated X Protein
• deltonin
• Poly(ADP-ribose) Polymerases
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Caspase 3
• Caspase 8

Topics

• Antineoplastic Agents, Phytogenic (chemistry, toxicity)
• Apoptosis (drug effects)
• Breast Neoplasms (metabolism, pathology)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Dioscorea (chemistry)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Poly(ADP-ribose) Polymerases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Spirostans (chemistry, toxicity)
• bcl-2-Associated X Protein (metabolism)